Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer
Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer
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DOI：
10.1073/pnas.0800019105
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发表时间：
2008-05-13
影响因子：
11.1
通讯作者：
Palumaa, Peep
中科院分区：
文献类型：
--
作者：
Banci, Lucia;Bertini, Ivano;Palumaa, Peep
人类蛋白质Cox 17含有三对半胱氨酸。在线粒体膜间隙（IMS）中，它以部分氧化的形式存在，具有两个S-S键和两个还原的半胱氨酸（HCox 17（2S-S））。HCox 17（2S-S）参与铜转移到人cochaperones Sco 1和Cox 11，这涉及细胞色素c氧化酶的组装。我们在这里表明，Cu（I）HCOx 17（2S-S），即，该蛋白质的载铜形式可以同时将铜（I）和两个电子转移到氧化态的人辅伴侣蛋白Sco 1（HSco 1），即，其金属结合半胱氨酸形成二硫键。结果是Cu（I）HSco 1和完全氧化的apoHox 17（3S-S），其然后可以被谷胱甘肽还原为apoHox 17（2S-S）。HSco 1/HCox 17（2S-S）氧化还原反应由铜转移热力学驱动。这些反应可能发生在体内，因为HSco 1可以发现在IMS内的部分氧化状态，与后者的可变的氧化还原特性相一致。HSco 1的电子转移偶联的金属化可以是IMS内的一种机制，用于金属向蛋白质的有效特异性转移，其中金属结合硫醇被氧化。相同的铜电子耦合转移反应不发生与人类同源物的Sco 1，HSco 2，动力学的原因，可能是由于缺乏一个特定的金属桥接的蛋白质-蛋白质复合物，这是相反，在Cu（I）HCox 17（2S-S）/HSco 1相互作用中观察到。
The human protein Cox17 contains three pairs of cysteines. In the mitochondrial intermembrane space (IMS) it exists in a partially oxidized form with two S-S bonds and two reduced cysteines (HCox17(2S-S)). HCox17(2S-S) is involved in copper transfer to the human cochaperones Sco1 and Cox11, which are implicated in the assembly of cytochrome c oxidase. We show here that Cu(I)HCox17(2S-S), i.e., the copper-loaded form of the protein, can transfer simultaneously copper(I) and two electrons to the human cochaperone Sco1 (HSco1) in the oxidized state, i.e., with its metal-binding cysteines forming a disulfide bond. The result is Cu(I)HSco1 and the fully oxidized apoHCox17(3S-S), which can be then reduced by glutathione to apoHCox17(2S-S). The HSco1/HCox17(2S-S) redox reaction is thermodynamically driven by copper transfer. These reactions may occur in vivo because HSco1 can be found in the partially oxidized state within the IMS, consistent with the variable redox properties of the latter compartment. The electron transfer-coupled metallation of HSco1 can be a mechanism within the IMS for an efficient specific transfer of the metal to proteins, where metal-binding thiols are oxidized. The same reaction of copper-electron-coupled transfer does not occur with the human homolog of Sco1, HSco2, for kinetic reasons that may be ascribed to the lack of a specific metal-bridged protein-protein complex, which is instead observed in the Cu(I)HCox17(2S-S)/HSco1 interaction.